Recent advances using zebrafish animal models for muscle disease drug discovery

Abstract

Introduction Animal models have enabled great progress in the discovery and understanding of pharmacological approaches for treating muscle diseases like Duchenne muscular dystrophy. Areas covered With this article, the author provides the reader with a description of the zebrafish animal model, which has been employed to identify and study pharmacological approaches to muscle disease. In particular, the author focuses on how both large-scale chemical screens and targeted drug treatment studies have established zebrafish as an important model for muscle disease drug discovery. Expert opinion There are a number of opportunities arising for the use of zebrafish models for further developing pharmacological approaches to muscle diseases, including studying drug combination therapies and utilizing genome editing to engineer zebrafish muscle disease models. It is the author’s particular belief that the availability of a wide range of zebrafish transgenic strains for labeling immune cell types, combined with live imaging and drug treatment of muscle disease models, should allow for new elegant studies demonstrating how pharmacological approaches might influence inflammation and the immune response in muscle disease.

Zebrafish models of sarcopenia

“…By 24 hpf, all segmental blocks of muscle, or myotomes (Box 1), are present, partitioned by tendon-like junctions, enabling the embryo to coil and even respond to touch. The muscle becomes fully differentiated by 48 hpf and the larva is freely swimming by 96 hpf (Baxter and Bryson-Richardson, 2018;Stickney et al, 2000;Maves, 2014).…”

Building dialogues between clinical and biomedical research through cross-species collaborations

“…One example is a chemical that was identified that partially ameliorated the muscle phenotype in dystrophin-null zebrafish models of the progressive muscle wasting disorder Duchenne’s muscular dystrophy, which currently is a terminal illness with no effective cure [71, 72]. These zebrafish chemical screen findings were further examined in a mouse model of Duchenne’s muscular dystrophy and found to similarly ameliorate the muscle phenotype in a mammalian animal model [73]. Such discoveries have great potential for translation into clinical applications for Duchenne’s muscular dystrophy by connecting basic research and clinical scientists through international clinical trial networks and patient registries such as the Translational Research in Europe-Assessment and Treatment of Neuromuscular Diseases (TREAT-NMD), Muscular Dystrophy Association, and the Registry of Muscular Dystrophy (Remudy) [47, 74].…”

A novel drug-combination screen in zebrafish identifies epigenetic small molecule candidates for Duchenne muscular dystrophy

“…Zebrafish are an outstanding model for DMD, particularly for screening and evaluating novel drug therapies (Bassett et al, 2003; Bassett and Currie, 2004; Berger et al, 2010; Maves, 2014; Widrick et al, 2019). A zebrafish dmd mutant strain, also known as sapje , has a nonsense mutation in exon 4 and is a dystrophin-deficient model of DMD (Bassett et al, 2003; Berger et al, 2010; Granato et al, 1996).…”

“…dmd zebrafish exhibit many aspects of human DMD pathology; in particular, skeletal muscle fibrosis and inflammation, including infiltration of mononuclear cells (Bassett and Currie, 2004; Berger et al, 2010). dmd zebrafish offer several advantages for screening and evaluating drugs, including being amenable to rapid and high-throughput screening and affording an exceptional range of approaches for assessing treatment outcomes (Kawahara et al, 2011; reviewed in Maves, 2014 and in Widrick et al, 2019). Zebrafish eggs can be rapidly produced in large numbers, the resulting embryos readily absorb drug compounds, and muscle development and structure can easily be observed in vivo through birefringence techniques (Berger et al, 2012; Granato et al, 1996; Kawahara et al, 2011).…”